ABNORMALITIES IN THE CITRATE CYCLE METABOLISM ARE ASSOCIATED WITH DECLINED INTRINSIC CAPACITY IN OLDER ADULTS

Abstract Background Aging is accompanied by a decline in physical and mental functions, manifested as the declines in intrinsic capacity. However, there is still a lack of understanding about the metabolic mechanisms underlying the declining intrinsic capacity. Objective: To explore the metabolic characteristics and pathways of the declines in intrinsic capacity with the assistance of metabolomics methods. Methods Our study recruited 38 participants in total. The Short Physical Performance Battery, Mini-Mental State Exam, 30-item Geriatric Depression Scale, self-reported hearing/visual impairment and Mini Nutritional Assessment were used to assess the five domains of intrinsic capacity respectively. The untargeted liquid chromatography-mass spectrometry-based metabolomics was performed on the serum of participants. Multivariate statistical analysis and pathway analysis were then implemented. Results Among the 38 participants aged 66.50±15.20 years, 22 were with the declines in at least one domain of intrinsic capacity. In the 349 identified metabolites, 35 were candidate biomarkers for declining intrinsic capacity with variable importance in the projection > 1.5 and p < 0.05. Citrate cycle, tryptophan metabolism, phenylalanine and tyrosine metabolism, and Arginine biosynthesis were significant pathways associated with the declines in intrinsic capacity. Conclusions Decreased intrinsic capacity is an age-related change with characteristic metabolomics features. Many pathways, especially the dysregulation of the citrate cycle metabolism, may be involved in the pathogenesis of intrinsic capacity decline.


PILOT STUDY TO PRAGMATICALLY EMBED CAREGIVER DEMENTIA EDUCATION AND SUPPORT IN HEALTH CARE SYSTEMS Richard Fortinsky, University of Connecticut Center on Aging, Farmington, Connecticut, United States
Evidence-based interventions offering meaningful benefits to informal caregivers of people living with dementia (PLWD) would be attractive to office-based practitioners if pragmatic linkages could be made between these interventions and outpatient care settings. This presentation will explain experiences and lessons learned in an ongoing pilot study in which we are: pragmatically identifying and inviting caregivers of PLWD to join online dementia education and support programs; collecting and storing caregiver outcomes data into electronic health records where these data are accessible to clinicians. Participating outpatient health care settings are a geriatrics practice at UConn Health and a memory care clinic at Emory Healthcare. Caregivers recruited at both sites participate in either Tele-Savvy or Caregiving During Crisis programs. Outcomes data will inform effects of program participation on caregivers' competence and stress, and help clinicians gain insights into caregivers' capacity to manage PLWD. Implementation evaluation strategies and results also will be discussed.

BUILDING CAPACITY FOR DEMENTIA CAREGIVER TOOLS AND PRAGMATIC TRIALS THROUGH STAKEHOLDER ENGAGEMENT Hillary Lum, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
Caregivers face challenges communicating and coordinating health-related needs on behalf of persons living with dementia (PLWD). This presentation will highlight capacity building activities at UCHealth, a large academic health system in Colorado and Wyoming, to prepare for pragmatic clinical trials to test integrated health informatics tools to improve the care of PLWD and their family caregivers. We will describe foundational activities of: 1) convening diverse patient and family caregivers to identify communication priorities and refine health informatics tools, 2) engaging health system leaders to develop a system-based value proposition, and 3) partnering with health informatics teams to adapt tools (i.e., dementia registry, refined patient portal tools) and implement reports of pragmatic outcomes. Through support as an NIA IMPACT Health Care System Scholar, we will discuss lessons learned related to highlighting the preferences of diverse caregivers, especially related to use of health informatics tools in the context of dementia care. People living with dementia (PLWD) are among the highest-need and highest-cost individuals because of the complexity, duration, and range of medical, behavioral, environmental, and social needs. There is a growing evidence base showing that family-centered active management approaches that include activation and empowerment of care partners are well suited to improve care quality and health-related outcomes, and have potential to curb high ADRD-related healthcare costs. This presentation will outline key experiences and lessons learned after a decade of work developing, adapting and embedding a comprehensive family-focused care management model called MIND at Home into practice. The work, supported in part by the IMPACT Collaboratory Health Care System Scholars Award to partner with Centene Corporation, a large managed care organization, illustrates two overriding principles: (1) the necessity of "meeting people and health systems where they are" (literally and figuratively), and (2) the importance of effectively matching intervention to outcome and context. Yiming Pan, Pan Liu, Yun Li, and Lina Ma, Xuanwu Hospital Capital Medical University, Beijing, Beijing, China (People's Republic) Background: Aging is accompanied by a decline in physical and mental functions, manifested as the declines in intrinsic capacity. However, there is still a lack of understanding about the metabolic mechanisms underlying the declining intrinsic capacity. Objective: To explore the metabolic characteristics and pathways of the declines in intrinsic capacity with the assistance of metabolomics methods.

ABNORMALITIES IN THE CITRATE CYCLE METABOLISM ARE ASSOCIATED WITH DECLINED INTRINSIC CAPACITY IN OLDER ADULTS
Methods: Our study recruited 38 participants in total. The Short Physical Performance Battery, Mini-Mental State Exam, 30-item Geriatric Depression Scale, self-reported hearing/visual impairment and Mini Nutritional Assessment were used to assess the five domains of intrinsic capacity respectively. The untargeted liquid chromatography-mass spectrometry-based metabolomics was performed on the serum of participants. Multivariate statistical analysis and pathway analysis were then implemented.
Results: Among the 38 participants aged 66.50±15.20 years, 22 were with the declines in at least one domain of intrinsic capacity. In the 349 identified metabolites, 35 were candidate biomarkers for declining intrinsic capacity with variable importance in the projection > 1.5 and p < 0.05. Citrate cycle, tryptophan metabolism, phenylalanine and tyrosine metabolism, and Arginine biosynthesis were significant pathways associated with the declines in intrinsic capacity.
Conclusions: Decreased intrinsic capacity is an age-related change with characteristic metabolomics features. Many pathways, especially the dysregulation of the citrate cycle metabolism, may be involved in the pathogenesis of intrinsic capacity decline.